This invention relates to the novel D-rhamnonoi-1,5-lactone and, more particularly, to the synthesis of D-rhamnono-1,5-lactone from D-gulonolactone.
In general, removal of the anomeric hydroxyl group from a pyranose sugar and replacement of the ring oxygen by a nitrogen atom reliably produces compounds which are effective inhibitors of the corresponding glycosidases [G. Legler, Adv. Carbohydr. Chem. Biochem. 48, 319 (1990); G. W. J. Fleet et al., Plagiarizing Plants: Aminosugars as a Class of Glycosidase Inhibitors, In: Bioactive Comoounds from Plants, p. 112-125, Wiley, Chichester (Ciba Found. Symp. 154), (1990); A. Straub et al., J. Org. Chem. 55, 3926 (1990); C.-H. Wong et al., Tetrahedron Lett. 32, 4867 (1991); G. Gradnig et al., Tetrahedron Lett. 32, 4889 (1991); P. S. Liu et al., Tetrahedron Lett. 32, 5853 (1991); L. E. Fellows and R. J. Nash, Sci. Progress 74. 245 (990)]. For example, deoxymannojirimycin (1), isolated from Lonchocarpus sericeus. [L. E Fellows et al., J. Chem. Soc. Chem. Commun., 977 (1979)] is a potent inhibitor of glycoprotein processing mannosidase I [U. Fuhrmann et al., Nature 307, 755 (1984); A. D. Elbein et al., Arch. Biochem. Biophys. 235, 579 (1984)], and a bovine .alpha.-L-fucosidase [S. V. Evans et al., Phytochemistry 24, 1953 (1985)]. The corresponding lactam, D-mannonolactam (2), is a powerful inhibitor of human lysosomal and rat epidodymal .alpha.-mannosidases, and of apricot .beta.-glucosidase [T. Niwa et al., J. Anibot. 37. 1579 (1984)]. Many mannopyranosidases are also inhibited by nitrogen analogues of mannofuranose. Thus, 1,4-dideoxy-1,4-iminomannitol (3) [G. W. J Fleet et al., J. Chem. Soc. Chem. Commun. 1240 (1984); G. W. J. Fleet et al., Tetrahedron Lett. 30, 7261 (1989)] is a strong of many mannosidases [Cenci di Bello et al., Biochem. J. 259, 855 (1989)] including a mannosidase of glycoprotein processing [P. F. Daniel et al., Glycoconjugate J. 6, 229 (1989); G. Palmartczky et al., Arch. Biochem. Biophys. 242, 35 (1958)]. Also, the 6-deoxyderivative (4) is an excellent inhibitor of human liver [A. J. Fairbanks et al., Tetrahedron 47, 131-138 (1991)] and other mannosidases. [M. J. Eis et al., Tetrahedron Lett. 26, 5398 (1985)].
Rhamnose (6-deoxymannose) residues are widely found intracellularly and extracellularly in plant tissues. The most common form found within the cell is as a component of a glycoside such as flavanoids, phenols, sterols, and coumarins; [G. Avigad, Sucrose and other Disaccharides. In "Plant Carbohydrates 1, Encylopedia of Plant Physiology", Vol. 13A, p. 217-347, Eds. F. A. Loewus and W. Tanner; Springer Verlag]; rhamnose is found typically as a disaccharide conjugate either as an .alpha. or .beta. rhamnopyranoside. The degradation of these glycosides is accomplished by a stepwise removal of monosaccharides by exoglycosidases. The aglycones are usually physiologically inactive compounds compared to the glycoside. These exoglycosidases would be an ideal system to test the stereospecificity of inhibition by rhamnose analogues, e.g. naringinase. Rhamnose is also found in intracellular polysaccharides of plants either as a component of cell walls or root mucilage; .alpha.-L-rhamnose is a major constituent of rhamnogalacturonan I [M. McNeil et al., Ann. Rev. Biochem. 53, 625 (1984)] while L-rhamnose is found in the .alpha.- and .beta.-linkages in rhamnogalacturonan II [T. T. Stevenson et al., Carbohydr. Res., 182, 207 (1988)]. If specific exorhamnosidases or endorhamnosidases could be assayed using the polymers as substrates, the use of rhamnose analogues to inhibit the enzyme can provide a useful tool for probing the structure of cell walls. ##STR1##